We have investigated the contribution of B-cells and antibodies to both the resistance and susceptibility to cutaneous leishmaniasis in mouse strains rendered B-cells depleted by treatment with goat anti-mouse IgM antisera from birth (Mu-suppressed). These studies confirm that immunity to cutaneous disease in a normally resistant mouse strain (C3H/HeJ) is antibody independent, but that unexpectly B-cells and/or antibodies are required for the evolution of suppressed delayed type hypersensitivity (DTH) and the consequent disease susceptibility of BALB/c mice. The data suggest the a B cell dependent T-cell which is critically involved in the suppressor pathway is absent in Mu-suppressed mice. We have also been studying the nature of Lesihmania promastigotes which are responsible for the initiation of infection within the vertebrate host. Promastigotes which emerge from the fly must become adapted to a potentially hostile vertebrate environment. It is known that culture derived promastigotes which have generally been used for study are readily killed by the non-immune vertebrate host. They are destroyed by fresh normal sera and by normal resident macrophages. We have found, however, the the virulence of culture derived L. tropica promastigotes changes dramatically depending upon their age in culture. Whereas the promastigotes taken from logarithmic phase cultures are completely destroyed within normal mouse peritoneal macrophages in vitro and are relatively avirulent in vivo, as the growth of promastigotes approaches stationary phase, their virulence both in vitro and in vivo steadily increases. In addition, stationary forms have significantly increased resistance to complement. We suggest that these changes which are seen during growth in culture mimic developmental events which occur within the sandfly, and that it is these transitional developmental forms which are required to initiate infection in the vertebrate host.